Irritable Bowel Syndrome with Diarrhea (IBS-D) MedDRA version: 20.1 Level: PT Classification code 10023003 Term: Irritable bowel syndrome System Organ Class: 10017947 - Gastrointestinal disorders MedDRA version: 20.1 Level: LLT Classification code 10060845 Term: Diarrhea predominant irritable bowel syndrome System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: Eluxadoline
Pharmaceutical Form: Tablet
INN or Proposed INN: Eluxadoline
CAS Number: 864821-90-9
Other descriptive name: ELUXADOLINE
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Allergan LTD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must provide written or verbal informed assent and the parent/guardian/LAR and caregiver must provide written informed consent before the initiation of any study-specific procedures. 2. Participant is a male or female outpatient, 6 to 17 years of age inclusive, at the time the participant provides assent for the study and parent/guardian/LAR has provided signed consent. 3. Participant is able to read and understand the assessments in the eDiary. If the participant is 6 to 11 years of age and does not meet this criterion, the interviewer-administered version of the eDiary must be used and the parent/guardian/LAR or caregiver who will be administering the interviewer-administered version of the eDiary must be able to read and understand the assessments in the eDiary and must undergo training. 4. Female participants of childbearing potential must have a negative serum pregnancy test at Visit 1 (screening) and a negative urine pregnancy test at Visit 3 (randomization) prior to dosing. 5. Female participants who have had their first menstrual period and are sexually active must agree to use a reliable form of contraception. Reliable contraception is defined as: a) Hormonal contraception (eg, oral contraceptive, contraceptive implant, or injectable hormonal contraceptive). b) Double-barrier method (eg, condom plus intrauterine device, diaphragm plus spermicide). 6. Participant has a diagnosis of IBS D as defined by the modified Rome IV child/adolescent criteria*: Must include all of the following: 1. Abdominal pain at least 4 days per month over at least 2 months associated with one or more of the following: a. Related to defecation b. A change in frequency of stool c. A change in form (appearance) of stool 2. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition 3. Participant has predominantly diarrheal stool symptoms defined as Bristol stool types 6 or 7 for >25% of bowel movements and Bristol stooltypes 1 or 2 for <25% of bowel movements that occur in the absence of laxatives *All criteria fulfilled for at least 2 months prior to Visit 1 (screening). 7. Participant has been compliant with the eDiary by completing both themorning and evening assessments for at least 8 out of the 14 days immediately preceding Visit 3 (randomization). 8. Participant has an average daytime abdominal pain score =2.0 over the 2 weeks prior to randomization. 9. Participant has at least 1 daytime bowel movement with a consistencyof Type 6 or Type 7 on the pediatric Bristol Stool Form Scale (p-BSFS) onat least 2 days per week during the 2 weeks prior to randomization that occurs in the absence of laxatives. 10. Participant has no clinically significant findings on a physical examination, vital sign assessment, electrocardiogram (ECG), and clinical laboratory tests (clinical chemistry panel, liver biochemical tests, complete blood count, urine drug screen, urinalysis) after providing informed assent and after written consent is obtained, but before receiving the first dose of study treatment. (A central laboratory will be used to evaluate all urine [except urine pregnancy tests] and blood samples and will utilize reference ranges specific to a participant's age and gender. ECGs will be performed and electronically transmitted to a central ECG laboratory for analysis by a pediatric cardiologist in accordance with the instructions provided by the central ECG laboratory. The Investigator will determine if a
Exclusion criteria
Exclusion criteria: Participants who meet any of the following criteria will not be eligible to participate in the study: 1.has no gallbladder 2.has had any of the following surgeries: a)Any abdominal surgery within the 3 months prior to trial; b)A history of major gastric, hepatic, pancreatic, or intestinal surgery 3.has known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction 4.has a history of pancreatitis; structural diseases of the pancreas, known or suspected pancreatic duct obstruction 5.has a history of cholecystitis within 6months before trial. 6.has known or suspected bile acid malabsorption. 7.is a current regular alcohol drinker and/or binge drinker, and/or has a history of alcoholism, alcohol abuse, or alcohol addiction, and/or intendsto consume alcohol during the trial. 8.has had chronic or severe constipation or sequelae from constipation, or known or suspected mechanical GI obstruction or pseudo obstruction.9.has had or current diagnosis of constipation with encopresis. 10.meets the child/adolescent Rome IV criteria of IBS with constipation,IBS with constipation and diarrhea (mixed), unspecified IBS, or functional constipation. 11.has had intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation. 12.has a history of hepatic impairment as defined by Child-Pugh Classification Grade A,B or C 13.has a history or current diagnosis of inflammatory or immune-mediated lower GI disorders including inflammatory bowel disease 14.has celiac disease,or a positive serological test for celiac disease and the condition has not been ruled out by endoscopic biopsy 15.has any congenital and/or acquired malabsorption syndrome 16.has a history of a microbiologically documented GI infection within 3 months prior to trial 17.has a known lactose or fructose intolerance 18.has a history of diverticulitis within 3 months prior to trial 19.has had within 5 years prior to trial or current evidence of laxative abuse 20.has a history of either hypo-or hyperthyroidism that is untreated or treated with medication at a dose that has not been stable for at least 3 months prior to trial. 21.Participant's diarrhea is deemed by the Investigator to be caused by infectious 22.has had or current evidence of blood in the stool 23.currently has both unexplained and clinically significant alarm symptoms and systemic signs of infection or colitis, or any neoplastic process 24.has a history or current diagnosis of eosinophilic gastroenteritis 25.has Cystic Fibrosis, and or any other causes of pancreatic exocrine insufficiency 26.is receiving enteral tube feeding 27.has a history of a cardiovascular event, including stroke, myocardial infarction, congestive heart failure, or transient ischemic attack within 6months prior to trial 28. has renal impairment or an unstable hepatic, metabolic, or hematologic condition 29.has a history of malignancy within 5 years before Screening, which includes any new diagnosis of malignancy or any treatment for or recurrence of a malignancy that was diagnosed 5 or more years prior. In order to be eligible for the study, participant must be malignancy free forthe past 5 years 30.has a history of immunodeficiency 31.has a history of drug abuse 32.has a positive urine drug result 33.has a weight and BMI less than the 3rd percentile. 34.has had an unintentional weight loss greater than or equal to 5%
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To explore the therapeutic effect of eluxadoline in treating IBS-D in pediatric participants 6-17 years of age. - To evaluate the pharmacokinetics (PK) of eluxadoline in pediatric patients with IBS-D. - To evaluate the safety and tolerability of eluxadoline in pediatric patients with IBS-D.;Secondary Objective: The results of this dose-ranging study will allow the selection of an optimal dose(s) of eluxadoline to evaluate in the subsequent confirmatory efficacy study. ;Primary end point(s): The primary efficacy assessment will be the change from baseline in the 24-hour (combined daytime and nighttime) daily stool consistency averaged over the 4-week Treatment Period.;Timepoint(s) of evaluation of this end point: Throughout the study Over the 4-week period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary change-from-baseline efficacy parameters include change from baseline in the 4 week average for daily daytime stool consistency scores and for nighttime stool consistency. scores, separately, during the Treatment Period. Additional, secondary change from baseline efficacy parameters include change from baseline in the 4 week average for daytime, nighttime and 24 hour (combined daytime and nighttime),) abdominal pain severity, bowel movement frequency, and urgency-free days in a week, and number of fecal incontinence-free days in a week during the Treatment Period. The secondary efficacy parameters evaluating change-from-baseline will be analyzed using an ANCOVA model similar to the one defined for the primary efficacy parameter. ;Timepoint(s) of evaluation of this end point: throughout the study 4 week | — |
Countries
Bulgaria, Canada, Germany, Hungary, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactAllergan Ltd EU Regulatory Dept
Allergan Ltd
Outcome results
None listed